Impact of Platelets and Fresh Frozen Plasma in Contrast to Red Cell Concentrate on Unstimulated and Stimulated Cytokine Release in an <i>In Vitro</i> Model of Transfusion

Schneider, Sven; Rensing, Hauke; Gräber, Stefan; Kreuer, Sascha; Kleinschmidt, S.; Kreimeier, Simone; Müller, Patrick; Mathes, Alexander; Biedler, A.

doi:10.1111/j.1365-3083.2009.02278.x

Cited by 40 publications

(49 citation statements)

References 31 publications

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“…In addition, in vitro allogeneic PRBC transfusion appears to have the potential to promote polymorphonuclear cell-mediated cytotoxicity and to suppress neutrophil locomotion (16) and apoptosis (17). Our findings of significant increases in proinflammatory cytokines after transfusion are in keeping with both in vitro evidence for induction of pro-and anti-inflammatory cytokines following PRBC exposure (18,19) and adult in vivo data (20). Specifically, PRBC transfusion has been demonstrated to result in significant increases in TNF-α (19) and IL-8 (21).…”

Section: Discussionsupporting

confidence: 77%

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

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Background: Transfusion of packed red blood cells (PRBcs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBc transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant. Methods: One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2-4 h after transfusion, as well as in the donor pack. results: Median (range) age at transfusion was 18 (14-39) days with the pretransfusion hemoglobin level at 9.8 (7.4-10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. a similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001). conclusion: Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBcs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation. t ransfusion of blood products is not benign. In adults, transfusion is an independent predictor of death and is associated with an increased incidence of multiorgan system failure, length of hospital stay, infection risk, and modulation of the immune system (1,2). Although the mechanisms underlying these associations are yet to be comprehensively characterized, a two-hit model of posttransfusion injury has been proposed (3). In the clinical setting of an underlying inflammatory state priming the recipient's immune system, transfusion of packed red blood cells (PRBCs) may trigger immune cell activation and related immunomodulation, resulting in frank inflammation (4). This transfusion-related immunomodulation (TRIM), encompassing not only adverse proinflammatory and immunosuppressive responses but also the whole spectrum of posttransfusion effects on organs and tissues, has been proposed to underlie much of the increased transfusionassociated morbidity and mortality seen in adults (4).In the neonatal population, there is an increasing awareness of the excess morbidity and mortality associated with PRBC transfusions (5,6). PRBC transfusions have been implicated in the development of problems not encountered in the adult population, including chronic lung disease (7), retinopathy of prematurity (8), and necrotizing enterocolitis (9,10), with the incidence and severity of these conditions correlating with the number and volume of PRBC tran...

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Section: Discussionsupporting

confidence: 77%

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

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“…An in-vitro study using a whole blood model reported increased interleukin (IL)-10 production and reduced tumour necrosis factor (TNF)-α production by the overall leukocytes in the culture supernatant following 24 h exposure to either autologous or allogeneic PRBC [81]. Similar studies consistently report suppression of TNF-α and augmentation of IL-10 responses following exposure to PRBC [89] or PRBC supernatants [85]. supernatants also augmented IL-6 production [85].…”

Section: In-vitro and In-vivo Models Of Prbc Transfusion (Related To mentioning

confidence: 90%

“…The potential for PRBC to modulate recipients' immune response and impact patient outcomes has been studied using in-vitro [79][80][81][82][83][84][85][86][87][88][89] and in-vivo [90] models. An in-vitro study using a whole blood model reported increased interleukin (IL)-10 production and reduced tumour necrosis factor (TNF)-α production by the overall leukocytes in the culture supernatant following 24 h exposure to either autologous or allogeneic PRBC [81].…”

Section: In-vitro and In-vivo Models Of Prbc Transfusion (Related To mentioning

confidence: 99%

“…In addition monocyte production of IL-12 was suppressed following exposure to PC with LPS [167]. In another study, overall leukocyte production of pro-inflammatory TNF-α and anti-inflammatory IL-10 was increased following exposure to PC alone with TNF-α reduced in the model of PC and LPS [89]. Recently, Perros et al (2015) reported that PC supernatant modulated mDC responses and the overall inflammatory response [168].…”

Section: Introductionmentioning

confidence: 96%

“…In-vitro studies demonstrate modulation of monocyte [86] and overall leukocyte [81,85,89] inflammatory responses following exposure to PRBC or PRBC components. These studies consistently report suppression of TNF-α and augmentation of IL-10 responses.…”

Section: Introductionmentioning

confidence: 99%

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Characterisation of dendritic cell immune profile in models of transfusion

Ki¹

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Blood transfusion modulates recipients' immune responses sometimes resulting in poor clinical outcomes. Further, transfusion with blood products at date-of-expiry has been associated with exacerbation of this concerning problem. In-vitro studies have demonstrated exposure to packed red blood cell (PRBC) and platelet products modulate the responses of leukocytes, however, there are limited studies on the impact of transfusion on dendritic cells (DC). Despite DC being central to the immune response, their role in transfusion-related immune modulation remains largely undefined. I hypothesised that exposure to blood components changes DC phenotype and function, which could be one mechanism underpinning transfusion-related immune modulation. The potential for blood components (PRBC, buffy-coat-derived platelet concentrates (PC) and cryopreserved platelets (cryo-PLT)) to modulate responses of myeloid dendritic cells ii whether blood components exposing F-actin for Clec9A ligation were present within the blood product. rhClec9A did not bind fresh or stored PRBC, and this outcome was supported by the lack of detection of F-actin. Although, no binding of rhClec9A to PC or cryo-PLT was demonstrated, F-actin was detected on both types of platelet products. As binding of rhClec9A to PRBC, PC or cryo-PLT was not detected, EDTA blood collection tubes were used for the remainder of the study under the premise that lack of expression of this receptor would not impact on outcomes in my transfusion models.I assessed the impact of fresh and/or stored blood products on mDC and BDCA3 + DC surface antigen and inflammatory profile using a human in-vitro whole blood model of transfusion. In parallel, to model the processes associated with viral or bacterial infection, polyinosinic:polycytidylic acid (polyI:C) or lipopolysaccharide (LPS) was added respectively. Exposure to PRBC and PC predominately suppressed surface antigen expression (CD40, CD80, CD83 and CD86) and inflammatory mediator production (interleukin (IL)-6, IL-8, IL-12, tumour necrosis factor-α and interferon-gamma inducible protein-10 or IL-10) on both DC subsets. These changes were often more evident in the presence of polyI:C and LPS, and when DC were exposed to stored PRBC. Similar modulation was evident for BDCA3 + DC when exposed to cryo-PLT alone and cryo-PLT in the presence of polyI:C and LPS. The impact of blood transfusion on the overall inflammatory response by leukocytes was also examined. The immunomodulatory effect of transfusion in-vitro was more pronounced in the presence of polyI:C and LPS. For PRBC, an additional erythrophagocytosis assay was conducted where the uptake of stored PRBC by mDC and BDCA3 + DC was significantly increased in comparison to fresher PRBC.This study provided the first evidence that exposure of PRBC, PC and cryo-PLT modulates mDC and/or BDCA3 + DC maturation and activation. The changes were more pronounced when modelling processes associated with concurrent viral or bacterial infection.Experimental evidence suggested that mod...

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Impact of intraoperative blood salvage on monocyte subsets alteration and intracellular tumor necrosis factor‐α production

Bomberg

Volk

Biedler

et al. 2017

J Biomedical Materials Res

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Venous: venous patient blood (n = 20). Native: mixed salvaged native blood (n = 20). Filtered: mixed salvaged leukocyte filtered blood (n = 20). Irradiated: mixed salvaged irradiated blood (n = 20). The frequency of the surface receptors CD14, HLA-DR, and intracellular tumor necrosis factor (TNF)-α on peripheral blood mononuclear cells was analyzed by fluorescence-activated cell sorting analysis. The frequency of unstimulated CD14 and CD14 cells as well as unstimulated HLA-DR and TNF-α positive monocytes was comparable between venous and filtered salvaged blood. However, native and irradiated salvaged blood increased compared with venous (p < 0.05) and filtered salvaged blood (p < 0.05) for unstimulated CD14 cells, HLA-DR, and TNF-α positive monocytes. Stimulated intracellular TNF-α positive monocytes were decreased in native, filtered, and irradiated salvaged blood compared with venous blood (p < 0.05). Processing perioperative salvaged blood with leukofiltration minimizes the influence on monocytes activation compared with native and irradiated salvaged blood. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 815-821, 2018.

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Impact of Platelets and Fresh Frozen Plasma in Contrast to Red Cell Concentrate on Unstimulated and Stimulated Cytokine Release in an In Vitro Model of Transfusion

Cited by 40 publications

References 31 publications

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Characterisation of dendritic cell immune profile in models of transfusion

Impact of intraoperative blood salvage on monocyte subsets alteration and intracellular tumor necrosis factor‐α production

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